ALX40-4C is also an antagonist of the chemokine receptor CXCR4 and binds to the second extracellular loop of this receptor. (Ala13)-apelin-13 is the first reported functional antagonist that blocks the hypotensive actions of apelin in a dose dependent manner. However, pIC50 values were not reported in this study [24].

The apelin receptor gene (APLNR) has been identified as one of a number of genes necessary to confer suceptibility of cancer cells to immunotherapy (i.e. T cell recognition and cytolysis) [36]. This effect is likely mediated by apelin receptor/JAK1 upregulation of the IFN-γ response that appears to promote antigen processing and presentation by tumours, and which improves the ability of T cells to recognize and attack the cancer cells. Defects in IFN-γ signalling is a recognised mechanism underlying resistance to immunotherapy [28]. The authors of [36] show that functional loss of APLNR in mouse models reduces the efficacy of immunotherapies (both adoptive cell transfer and checkpoint blockade) and is indicative of poor prognosis.